Hydrochloric Acid → (S)-8-((2-amino-4-methylpentyl)oxy)-9-cyclopropyl-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398300Notes

Reaction equation

HRID 1398300 reaction equation
[CH:1]1([C:4]2[C:19]([O:20][CH2:21][C@@H:22]([NH:27]C(=O)OC(C)(C)C)[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:18][C:7]3[N:8]([CH3:17])[C:9](=[O:16])[C:10]4[C:15]([C:6]=3[CH:5]=2)=[CH:14][CH:13]=[N:12][CH:11]=4)[CH2:3][CH2:2]1.Cl.O1CCOCC1>CO>[NH2:27][C@@H:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:21][O:20][C:19]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[N:8]([CH3:17])[C:7]=2[CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710310(S)-tert-butyl (1-((9-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213725(S)-8-((2-amino-4-methylpentyl)oxy)-9-cyclopropyl-6-methylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 17.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((9-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (60 mg, 0.129 mmol) in MeOH (4 mL), at 0° C. was added a 4M solution of HCl in 1,4-dioxane (2 mL, 8 mmol). The resultant solution was stirred for 2 h at RT. The methanol was removed under reduced pressure and the residue was extracted with ethyl acetate (2×5 mL). The organic phase was washed with saturated aqueous NaHCO3 (2×5 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel column (MeOH—CHCl3) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-cyclopropyl-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (8 mg, 0.022 mmol, 17% yield) as an off-white solid. LC/MS (ESI) m/z 366.2 [(M+H)+, calcd for C22H28N3O2 366.2]; LC/MS retention time (method B): tR=1.34 min. HPLC retention time (method B): tR=4.87 min and HPLC retention time (method A): tR=9.18 min. 1H NMR (400 MHz, CDCl3) δ ppm 9.47 (s, 1H), 8.75 (d, J=5.7 Hz, 1H), 8.28 (d, J=5.7 Hz, 1H), 7.96 (s, 1H), 7.06 (s, 1H), 4.27 (m, 1H), 4.06-4.15 (m, 1H), 3.84 (s, 3H), 3.38-3.48 (m, 1H), 2.23-2.38 (m, 1H), 1.83-1.94 (m, 1H), 1.56-1.67 (m, 1H), 1.46-1.55 (m, 1H), 1.00-1.08 (m, 6H), 0.79-0.94 (m, 4H).

Workup

  1. customThe methanol was removed under reduced pressure
  2. extractionthe residue was extracted with ethyl acetate (2×5 mL)
  3. washThe organic phase was washed with saturated aqueous NaHCO3 (2×5 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica-gel column (MeOH—CHCl3)

Sources & evidence

ORD record
ord-a818e4eb6b4146b4a3e094e928a563b1
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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